GENOTYPIC DIVERSITY AND PRIMARY DRUG RESISTANCE OF MYCOBACTERIUM TUBERCULOSIS STRAINS IN THE NOVGOROD REGION OF RUSSIA IN THE COVID-19 PRE-PANDEMIC PERIOD



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Abstract

In the Novgorod region, the proportion of multidrug-resistant tuberculosis (MDR-TB) among newly diagnosed patients increased from 29.0% in 2014 to 41.9% in 2023. In 2018, the region was among the regions with the highest proportions of MDR-TB among HIV-positive patients. Molecular genetic monitoring of the circulation of Mycobacterium tuberculosis strains in the regions has not yet been studied. Our study aimed to assess the genetic diversity of M. tuberculosis strains and identify the genotypes of pathogens associated with multidrug resistance in the Novgorod region. Eighty-nine M. tuberculosis strains isolated in 2019 from newly diagnosed tuberculosis patients (21 coinfected with HIV) were studied. Strains were assigned to the Beijing genotype, its main sublineages and subtypes based on the analysis of specific genetic markers. MIRU-VNTR typing was performed for the Beijing strains, and the Hunter-Gaston diversity index (HGI) was calculated. The remaining strains were spoligotyped and assigned to genetic families according to the international SITVIT2 database. A total of 48.3% of strains were found to belong to the Beijing genotype (L2) of the modern sublineage. Among the non-Beijing strains, genotypes of the Euro-American lineage (L4) were distinguished: LAM (24.7%), Ural (12.4%), Haarlem (5.6%), T (7.9%). The shares of Beijing subtypes in the reduction of the strain sample were: B0/W148 (20.2%), Central Asian/Russian (19.1%), CAO (3.4%). The B0/W148 subtype was associated with HIV status (38.1% versus 14.7%; p = 0.029). MDR constituted 46.1% of strains; MDR was more common in HIV-positive patients (76.2% versus 36.8%; p = 0.002). All B0/W148 and CAO strains were MDR, while Central Asian/Russian strains accounted for 47.1%, non-Beijing strains  — 26.1%. Most MDR strains had mutations in the rpoB Ser531Leu and katG Ser315Thr genes, 24.4%  –  gyrA gene. MIRU-VNTR typing of 43 Beijing strains revealed 16 profiles; the largest clusters were 100-32 (32.6%; all MDR) and 94-32 (16.3%). B0/W148 strains were characterized by the highest clustering (HGI 0.40). Thus, the heterogeneous M. tuberculosis population in the Novgorod region is dominated by the Beijing genotype while its B0/W148 subtype included only MDR strains and is associated with HIV coinfection.

About the authors

A. Vyazovaya

St. Petersburg Pasteur Institute, St. Petersburg, Russian Federation

Email: annavyazovaya@gmail.com

DSc (Biology), Leading Researcher, Laboratory of Molecular Epidemiology and Evolutionary Genetics

Russian Federation

A. Yu. Chilikina

St. Petersburg Pasteur Institute, St. Petersburg, Russian Federation;
ITMO University, St. Petersburg, Russian Federation

Email: plm00_00@mail.ru

student, Faculty of Biotechnologies ITMO University, St. Petersburg, Russian Federation; preparatory, Laboratory of Molecular Epidemiology and Evolutionary Genetics, St. Petersburg Pasteur Institute, St. Petersburg, Russia

Russian Federation

A. Petrova

Novgorod Clinical Specialized Center of Phthisiopulmonology, Veliky Novgorod, Russian Federation;
Yaroslav-the-Wise Novgorod State University, Veliky Novgorod, Russian Federation

Email: baclab_nkscfp@mail.ru

Head of the Bacteriology Laboratory, Novgorod Clinical Specialized Center of Phthisiopulmonology, Veliky Novgorod, Russian Federation; assistant of department of Specialized therapy, Novgorod State Univesity, Veliky Novgorod, Russian Federation

Russian Federation

O. Fedotova

Novgorod Clinical Specialized Center of Phthisiopulmonology, Veliky Novgorod, Russian Federation

Email: baclab_nkscfp@mail.ru

Doctor of Clinical Laboratory Diagnostics, Novgorod Clinical Specialized Center of Phthisiopulmonology, Veliky Novgorod, Russian Federation

Russian Federation

E. Yukhnova

Novgorod Clinical Specialized Center of Phthisiopulmonology, Veliky Novgorod, Russian Federation

Email: baclab_nkscfp@mail.ru

Paramedic of the Organizational and Methodological Department, Novgorod Clinical Specialized Center of Phthisiopulmonology, Veliky Novgorod, Russian Federation

Russian Federation

A. Gerasimova

St. Petersburg Pasteur Institute, St. Petersburg, Russian Federation

Email: kantarelle@mail.ru

Junior Researcher, Laboratory of Molecular Epidemiology and Evolutionary Genetics, St. Petersburg Pasteur Institute, St. Petersburg, Russian Federation

Russian Federation

N. Solovieva

St. Petersburg Research Institute of Phthisiopulmonology, St. Petersburg, Russian Federation

Email: baclab@spbniif.ru

PhD (Medicine), Head of the Bacteriology Laboratory, St. Petersburg Research Institute of Phthisiopulmonology, St. Petersburg, Russian Federation

Russian Federation

V. Zhuravlev

St. Petersburg Research Institute of Phthisiopulmonology, St. Petersburg, Russian Federation

Email: jouravlev-slava@mail.ru

PhD (Medicine), Leading Researcher, Coordinator of Laboratory Diagnostics Department, St. Petersburg Research Institute of Phthisiopulmonology, St. Petersburg, Russian Federation

Russian Federation

I. Mokrousov

St. Petersburg Pasteur Institute, St. Petersburg, Russian Federation

Email: imokrousov@mail.ru

DSc (Biology), Head of the Laboratory of Molecular Epidemiology and Evolutionary Genetics, St. Petersburg Pasteur Institute, St. Petersburg, Russian Federation

Russian Federation

A. Karpov

Novgorod Clinical Specialized Center of Phthisiopulmonology, Veliky Novgorod, Russian Federation;
Yaroslav-the-Wise Novgorod State University, Veliky Novgorod, Russian Federation

Author for correspondence.
Email: nkscfp@mail.ru

DSc (Medicine), Professor, Head doctor, Novgorod Clinical Specialized Center of Phthisiopulmonology, Veliky Novgorod, Russian Federation; Head of Specialized therapy department, Novgorod State Univesity, Veliky Novgorod, Russian Federation

Russian Federation

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